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CHAHAT RANA

26 March 2021

NEWS / HEALTH

The bad science and poor ethics of Patanjali’sCoronil research

Ramdev along with the union health minister Dr Harsh Vardhan and Nitin Gadkari during the release ofresearch papers on Patanjali Coronil medicine for Covid-19 in February. RAJ K RAJ / HINDUSTAN TIMES

(/covid-19)

On 19 February, Patanjali Ayurved, the packaged consumer goods

company founded by self-styled yoga guru Baba Ramdev, announced the

publication of a research paper on its COVID-19 medicine called Coronil.

Doctors across India strongly protested both the manner in which the

announcement was made—Harsh Vardhan, the union health minister,

presided over it—and the company’s claim that the research showed

Coronil was e�ective against COVID-19. Three days after the event, the

Indian Medical Association issued a press release that said Patanjali’s

claims amounted to “blatant deceiving of the people of the country.” A

month later, the Pune Mirror reported

(https://punemirror.indiatimes.com/pune/crime/criminal-case-against-

patanjali-on-coronil/articleshow/81556528.cms), a law student in Pune

�led a criminal case against Ramdev and Acharya Balkrishna, the

chairman of Patanjali Ayurved and an author of the Coronil study, on

grounds of cheating, criminal conspiracy, and a malignant act likely to

spread infection of disease dangerous to life.

On 4 February, the journal Phytomedicine published

(https://www.sciencedirect.com/science/article/pii/S0944711321000362?

via%3Dihub) a paper describing a randomised control trial testing the

e�cacy of Patanjali’s Coronil kit. The study was authored by employees

of Patanjali and doctors from the National Institute of Medical Sciences,

a private medical college in Rajasthan. The kits consist of Coronil tablets

made from ayurvedic herbs ashwagandha, giloy and tulsi. It also includes

Patanjali’s swasari vati, which a mixture of more than a dozen medicinal

herbs that is supposed to treat colds and coughs, and anu taila, which is

another mixture of herbs pressed into an oil which the Patanjali website

claims has “multifarious bene�ts.” The study’s purpose was to evaluate

“the impact of traditional Indian Ayurvedic treatment regime on

asymptomatic patients with COVID-19 infection.”

The team conducted a double-blind randomised control trial. This

means that volunteers were randomly assigned to either the treatment

arm (in which they received medicines from the Coronil kit) or the

placebo arm. Neither the research team nor volunteers themselves knew

which arm they were in. The study’s endpoints were to test viral loads

through RTPCR on days one, three and seven. The trial also tested levels

of two types of proteins secreted by the immune system called cytokines

—interleukin-6 or IL-6 and tumor necrosis factor alpha or TNF-α—in

the patients’ blood. In severe COVID-19 infections, sensitive immune

systems have been found to respond in the form of cytokine storms that

can produce severe, even fatal e�ects. Patanjali’s study also measured the

levels of high sensitivity C-reactive protein or hs-CRP, which is produced

by the liver when there is in�ammation in the body.

According to the results, by day seven of the trial, hundred percent of the

people in the treatment arm recovered compared to 60 percent in the

placebo arm. Recovery was not measured by an eradication of symptoms

alone but by virological clearance, which is when patients were clear of

all virus as con�rmed by RTPCR tests.

I spoke with two medical experts who have closely evaluated the study

and found major methodological �aws, which in turn make the study’s

results contentious. Cyriac Abby Philips, a hepatologist at Kerala’s

Ernakulam Medical Centre, who has been closely monitoring the

scienti�c claims made in favour of Coronil, told me that the foremost

�aw was the relatively small sample size of 95 patients. “The authors have

not calculated the sample size required to adequately prove e�cacy and

safety,” he said. The study included only 95 patients of which 45 were in

the treatment arm and 50 were in the placebo arm. A larger sample size

leaves less room for error, while a smaller sample size can amplify a false

result. Jammi Nagaraj Rao, an independent public health physician and

epidemiologist who served over 25 years in the United Kingdom’s

National Health Service, further explained the problems of too small a

sample size. “For example, if you see a positive trend due to the medical

intervention and if it is consistent in a larger sample size, there is less of a

chance of it being a false trend or an outlier,” he said. Conversely, a small

sample size limits the chance of investigators observing an unexpected

result. “This is what we call the type 2 statistical error, which is an error

of omission. In a smaller sample size, one might miss out on results

which they might have observed in a bigger sample,” Rao added. To put

trial sizes into context, the World Health Organization’s trial

(https://www.nejm.org/doi/full/10.1056/NEJMoa2023184) to test four

repurposed antiviral drugs enrolled 11,330 hospitalised COVID-19

patients from 405 hospitals across 30 countries. P�zer tested its vaccine

on more than 43,000 participants randomised into intervention and

placebo arms for its phase two and three trials.

The second major �aw in the study was with the endpoints. All clinical

studies should have a well-de�ned endpoint. The primary endpoint of a

study is the result that points to the most signi�cant question the trial is

trying to answer. In the Coronil study, this endpoint was viral clearance.

“Here, the authors have only measured viral clearance, which is not equal

to resolution of disease,” Philips. Viral clearance denotes the absence of

virus in the body and resolution of disease refers to an end of all

symptoms. A more valuable clinical endpoint for the study is to measure

the time it takes for symptoms to resolve and for patients to feel healthy

again. “For an acute disease like COVID-19, looking at recovery time,

reduced mortality rate, reducing the need for intensive care—these are

the endpoints that matter,” Rao said. “Viral clearance occurs on its own

through the passage of time, but medical intervention should intend to

save lives here.” Most clinical trials for COVID-19 therapy, such as

the recovery trial (https://www.recoverytrial.net/results) in the UK which

tests various repurposed drugs and therapies on patients, seek reduction

in mortality rates in hospitalised patients as a primary endpoint.

Rao admitted that there was some value in measuring viral clearance in

patients after a medical intervention for epidemiological purposes. “It

will help reduce overall infectivity in the population I suppose,” he said.

“In diseases like typhoid and tuberculosis this was important, because

often people weren’t allowed to assimilate back in society until they were

clear of the infection completely, even if their symptoms had receded.”

However, for the current pandemic, India’s public health strategy does

not focus on eradicating viral load. “Each individual needs to wear masks

and practice social distancing. We all have to assume that any of us can

be a carrier of the infection and take precautions accordingly. So, the

focus is not so much on killing the virus, but on making sure fewer

people die from the disease,” Rao explained.

Another reason why viral clearance is not a great marker for the

ayurvedic treatment’s e�cacy is that the study only recruited

asymptomatic COVID-19 patients. Rao argued that asymptomatic

patients, whether in the treatment or the placebo group, had mild

infections and were bound to clear the virus from their systems without

medical intervention. “It is a vague endpoint,” Rao emphasised. “How do

we know that all the patients enrolled in the trial would have tested

negative at the end of day seven anyway, without any ayurvedic

intervention?” To illustrate this point, let us imagine that you are in the

�rst car at a tra�c intersection waiting for the light to turn green.

Behind your car is a truck honking at you while the light is red. After half

a minute, green comes on, you put your car in gear and move ahead. You

would have done this regardless of honking from behind. But the truck

driver thinks his persistence with the horn is what made you move. The

Coronil study only established that the medicine is as e�ective as the

truck in our analogy. Coronil was claiming to push the COVID-19

infection along a path that it would have naturally taken anyway.

It was also unclear when each of the enrolled asymptomatic patients was

�rst exposed to the virus. Each patient was possibly enrolled while they

were at di�erent stages of the disease. So, day three for one patient, could

actually be day seven for another. This error is called lead-time bias.

“Such inclusion could falsely give us the impression that patients on

treatment improved earlier than the ones receiving placebo,” Philips

said.

If the trial investigators had decided to enroll symptomatic patients, then

the day on which symptoms showed up could have been the standardised

day one. “The convention is to always use symptomatic patients,” Rao

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said. “With asymptomatic patients there is no way of knowing when

exactly they contracted the disease. Some of the patients enrolled in the

trial might have a lead in terms of having contracted the virus much

before the others. This also means that this patient will shed their viral

load before others. Suppose most of the patients in the intervention arm

have this lead, then there is a chance that the trial is boasting of a false

positive result.”

The secondary endpoints were levels of IL-6, TNF-α and hs-CRP, all

which are markers of the extent of in�ammation. According to the paper,

these were measured to assess the e�ect of the Ayurvedic regime on

in�ammation. “Not only is it unusual for asymptomatic patients to have

high levels of cytokines, but also the fact that due to the lead time bias,

each patient will have di�erent levels of IL-6 to begin with,” Rao pointed

out.

The study acknowledged that “IL-6 was found to be reduced in the

treatment group, although the reduction was not statistically signi�cant

in comparison to the placebo group, most likely, due to small sample

size”. Despite this concession, the paper concluded that “average fold

changes in serum levels of hs-CRP, IL-6 and TNF-α in the treatment

group were respectively, 12.4, 2.5 and 20 times lesser than those in the

placebo group at day 7”. In other words, the authors implied that the rate

of increase in in�ammatory markers were much less in the treatment

group as compared to the placebo group. Philips said that using any of

the in�ammatory markers as secondary endpoints was misguided.

“These are soft endpoints because they do not have a speci�c association

with a COVID-19 infection, they can occur due to any serious injury,

stress or infection in the body. The levels of these markers alone cannot

reveal anything regarding how sick a patient is,” he explained. In other

words, even when levels of these in�ammatory markers are low in the

patient’s body, it does not suggest that the patient has recovered.

Reciprocally, if someone has high levels of such markers in their body, it

does not necessarily suggest that they have a severe COVID-19 infection.

“The problem is not necessarily that these markers were measured, but

that these weren’t complimented with clinical and radiological

endpoints,” Philips continued. A clinical endpoint would be a resolution

of symptoms or decreased number of days under intensive care, but since

the trial enrolled only asymptomatic patients, it could not assess such

clinical endpoints. A radiological endpoint such as a computed

tomography or CT scan of the lungs could be a useful end point to study

even asymptomatic patients. However, the Patanjali study did not

include any data on CT scans of enrolled patients.

Then there are the results. The perfect recovery rate of hundred percent

and the absence of any reported adverse event is very rare, even

impossible, in a carefully conducted clinical trial. “I can see how the

hundred percent recovery rate arises from the fact that they had a �awed

trial design, where the endpoint is viral clearance and there is a lead time

bias, but it is hard to believe that no patient reported adverse events or

side e�ects,” Rao said. Even patients in the placebo arm of trials often

report side e�ects and symptoms. “Not because the placebo causes these

side e�ects, but because if you ask patients to report any symptoms, they

will have observed at least some physical manifestation or change in their

body which they �nd unusual,” Rao said. The absence of reported

adverse events, according to Rao, was more a sign of a poorly designed

and implemented trial protocol, than evidence for the safety of the

ayurvedic medicine.

“Without good study power and sample calculation and speci�cally

including adverse events as a secondary end point, one will tend to miss

drug-related side e�ects,” Philips said. The study claims that the

“Ayurvedic medicines studied in this trial �t well with this requirement:

these are safe without any observed side-e�ects, can be distributed en

mass and are e�ective against asymptomatic to mild cases.” Philips said

that Patanjali’s Coronil kit included substances with known side e�ects.

A study on ashwagandha, a medicinal plant which is a key ingredient in

the Coronil tablet, published in the journal Liver International in

February 2020, showed

(https://pubmed.ncbi.nlm.nih.gov/31991029/) how the medicine can

cause liver injury and toxicity. In December of 2020, Philips had tweeted

(https://twitter.com/drabbyphilips/status/1338512692747796480) results

of a test he had conducted on the Coronil tablet, which revealed that the

medicine contained higher than recommended levels of lead and

cadmium. “Ashwagandha has been shown to cause severe liver toxicity in

combination with other herbs in polyherbal formulations,” Philips

reiterated to me. “Swasari Ras alone or in combination with the other

components of Coronil kit are not studied on tissue lines, small animals

and in humans adequately to assess their safety. Also, the

pharmacokinetics and pharmacodynamics of this combination in

humans remain unknown. Hence direct use in humans as part of this

study was very unethical.”

Despite the inadequacies in the paper, government representatives

explicitly endorsed the Coronil kit. In the 19 February press conference,

Ramdev was �anked by two senior union ministers: Harsh Vardhan, the

health minister and Nitin Gadkari, the minister for micro, small and

medium enterprises. Endorsing the product and the Patanjali’s research

paper, Vardhan said, “Using this modern and scienti�c mechanism to re-

establish Ayurveda’s relevance in the world is a proud moment for India.”

Many sections of the medical community objected to the ministers’

presence at the press conference. In their letter

(https://twitter.com/just1doctorwala/status/1363744925641183232/photo/2)criticising

the false claims made by Patanjali, the IMA also condemned Vardhan’s

endorsement. The letter said that the health minister, being a doctor

himself, had violated the code of ethics according to which a physician

should not give any person an endorsement, approval or

recommendation for any drug or medicine. The IMA demanded an

explanation from Vardhan and claimed they would write to the National

Medical Commission seeking suo moto explanation for Vardhan’s blatant

disrespect towards the Medical Council’s code of conduct.

“Code of conduct or not, this explicit endorsement by the government

makes me very uncomfortable,” Rao said. “How can government o�cials

espouse such a treatment, which has not even been clinically

established?”

At the same press conference, Patanjali announced that the Central

Drugs Standard Control Organisation granted Coronil a certi�cate of

pharmaceutical product or a CoPP after the paper was published. India’s

guidelines for granting CoPP are based on the World Health

Organization’s guidelines on Good Manufacturing Practices

(https://www.who.int/teams/health-product-and-policy-

standards/standards-and-speci�cations/gmp) for medicinal products.

This certi�cate allows Patanjali to export Coronil to more than 158

countries. Various news portals inaccurately reported

(https://www.youtube.com/watch?v=MBJpx-

hzWdw&feature=emb_title&ab_channel=News18India) that the WHO

had “approved” or “certi�ed” Coronil as treatment for COVID-19. Such

rumours were fuelled by a number of identical tweets

(https://www.boomlive.in/fact-check/false-claims-go-viral-about-

patanjalis-coronil-approved-by-who-12061) stating that “Patanjali has

made history in the �eld of Ayurveda as Coronil has been recognised by

WHO as First Evidence based medicine for Corona.” The WHO was

quick to dismiss the rumours, tweeting

(https://twitter.com/WHOSEARO/status/1362755186112880646) that it

had “not reviewed or certi�ed the e�ectiveness of any traditional

medicine for the treatment of COVID-19.” I wrote multiple emails to

WHO’s regional o�ce for South East Asia that monitors public health in

India asking what they think about the promotion of alternative

therapies as treatment of COVID-19 in general and of Patanjali’s study in

particular. I received no response till the time this story was published.

Support The CaravanThe more you can help, the more we can do

As a valued subscriber, you are already a partner in ourmission to bring out fair and fearless journalism. At a timewhen the independent media faces unprecedentedchallenges, we ask you to extend your support further with aone-time or recurring contribution of any size you choose.Every contribution, big or small, helps us to investigate moreleads, to report on more crises, and to uphold the value oftruthful journalism in the service of democracy.

Patanjali’s poorly designed study and loud promotion of Coronil casts a

shadow on more substantive and relevant research into Ayurveda and

other traditional medicine. MS Valiathan, a renowned cardiologist who

has authored several articles and books on Ayurveda and a former

president of the Indian National Science Academy has studied the

convergence of modern biology and ayurveda as a scienti�c discipline.

He told me that it was possible to hold clinical research in Ayurveda to

the standards of modern science. “We need to design good clinical trials

to test these products,” he said. “There is a lot to gain from this school of

medicine, but we can’t just rely on anecdotal evidence and faith any

more. Research in Ayurveda should be modelled on the current standard

of clinical research.”

This reporting was supported by a grant from the Thakur Family Foundation.

Thakur Family Foundation has not exercised any editorial control over the

contents of this reportage.

CHAHAT RANA (/AUTHOR/37386) is a reporting fellow at The Caravan. 

KEYWORDS: Patanjali(/tag/patanjali) COVID-19(/tag/covid-19) WHO(/tag/who)

Ramdev(/tag/ramdev) Ayurveda(/tag/ayurveda)

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READER'S COMMENTS

Raina Rathore21 Apr, 2021

Chahat rana u only described what other articles are saying . Auseless article ...!!!!!

Abhi Shah30 Mar, 2021

Appreciate this very well written and researched abstract. Theepidemiologists’ concerns and the IMa for that matter too; are valid,logical and frankly speaking very honest in the face of most doctors.Kudos.

Dr Hemang Shah29 Mar, 2021

Caravan please stop nonsense. Ayurvedic science is always right.May be coronil required more research.

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